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Janet Markle, PhD

  • Assistant Professor

Departmental Affiliations

Contact Information

615 N. Wolfe Street
Room E5148
Baltimore, Maryland 21205

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MPH, University of Waterloo, 2014
PhD, University of Toronto, 2013
BSc, University of Western Ontario, 2006


The Markle Lab is interested in understanding genetic determinants of immunity. Our work sits at the crossroads of human immunology, genetics, and host-pathogen interactions.

For most infectious diseases, only a small fraction of children infected by a given microbe will go on to develop clinical disease. The huge inter-individual variability in response to primary infection in childhood results at least in part from variations in host genetic determinants of immunity. Over the past decades, next-generation sequencing technologies including whole exome sequencing (WES) have facilitated the discovery of hundreds of single-gene inborn errors of immunity, each giving rise to a unique spectrum of susceptibility to microbes. Similarly, only a minority of the population will experience autoimmunity or autoinflammation, and only a small subset of those will have severe and early-onset disease. It has been postulated (and in some cases, demonstrated) that severe early-onset autoinflammatory diseases have not only has a distinct phenotype, but also a unique monogenetic architecture, when compared to adult-onset polygenic diseases.

Our lab uses WES to discover monogenic errors of immunity in patients with infectious or autoinflammatory diseases. Then, we study the impact of these variants on the expression and/or function of the encoded proteins. We aim to thoroughly characterize the functional impact of each variant at the molecular and cellular levels, and to this end we use a combination of techniques in molecular biology, protein biochemistry, cell biology and immunology. We are particularly interested in applying this approach to novel settings, including the study of infection by Leishmania. Visceral Leishmaniasis (VL), also commonly called kala-azar, is a neglected tropical infectious disease caused by Leishmania parasites which mostly affects children. The pathogenesis of VL is complex, and the outcome of Leishmania infection can range from asymptomatic to fatal. We hypothesize that, similar to other severe infectious diseases previously studied by our team and our collaborators, the heterogeneity in clinical outcomes following Leishmania infection results from human genetic factors controlling susceptibility vs. resistance.

Honors and Awards

Senior Fellowship in Biomedical Science, The Charles H. Revson Foundation (2015-2017)

K99/R00 award recipient, NIAID (2017-2019)

The Willowcroft Foundation Award (2018)

  • Immunology
  • Genetics
  • Infection
  • Host-Pathogen interactions
  • Autoimmunity
  • Autoinflammation

Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Okada S*, Markle JG*, Deenick EK, Mele F, Averbuch D, Lagos M, Alzahrani M, Al-Muhsen S, Halwani R, Ma CS, Wong N, Soudais C, Henderson LA, Marzouqa H, Shamma J, Gonzalez M, Martinez-Barricarte R, Okada C, Avery DT, Latorre D, Deswarte C, Jabot-Hanin F, Torrado E, Fountain J, Belkadi A, Itan Y, Boisson B, Migaud M, Arlehamn CSL, Sette A, Breton S, McCluskey J, Rossjohn J, de Villartay JP, Moshous D, Hambleton S, Latour S, Arkwright PD, Picard C, Lantz O, Engelhard D, Kobayashi M, Abel L, Cooper AM, Notarangelo LD, Boisson-Dupuis S, Puel A, Sallusto F, Bustamante J, Tangye SG, Casanova JL. Science. 2015 PMID: 26160376 *equal contributions

  • Visceral leishmaniasis in two patients with IL-12p40 and IL-12R?1 deficiencies. Parvaneh N, Barlogis V, Alborzi A, Deswarte C, Boisson-Dupuis S, Migaud M, Farnaria C, Markle J, Parvaneh L, Casanova JL, Bustamante J. Pediatr Blood Cancer. 2017 PMID: 27873456.
  • The mutation significance cutoff: gene-level thresholds for variant predictions. Itan Y, Shang L, Boisson B, Ciancanelli MJ, Markle JG, Martinez-Barricarte R, Scott E, Shah I, Stenson PD, Gleeson J, Cooper DN, Quintana-Murci L, Zhang SY, Abel L, Casanova JL. Nat Methods. 2016 PMID: 26820543
  • The human gene damage index as a gene-level approach to prioritizing exome variants. Itan Y, Shang L, Boisson B, Patin E, Bolze A, Moncada-Vélez M, Scott E, Ciancanelli MJ, Lafaille FG, Markle JG, Martinez-Barricarte R, de Jong SJ, Kong XF, Nitschke P, Belkadi A, Bustamante J, Puel A, Boisson-Dupuis S, Stenson PD, Gleeson JG, Cooper DN, Quintana-Murci L, Claverie JM, Zhang SY, Abel L, Casanova JL. Proc Natl Acad Sci U S A. 2015 PMID: 26483451
  • The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to ?-papillomaviruses. de Jong SJ, Créquer A, Matos I, Hum D, Gunasekharan V, Lorenzo L, Jabot-Hanin F, Imahorn E, Arias AA, Vahidnezhad H, Youssefian L, Markle JG, Patin E, D'Amico A, Wang CQF, Full F, Ensser A, Leisner TM, Parise LV, Bouaziz M, Maya NP, Cadena XR, Saka B, Saeidian AH, Aghazadeh N, Zeinali S, Itin P, Krueger JG, Laimins L, Abel L, Fuchs E, Uitto J, Franco JL, Burger B, Orth G, Jouanguy E, Casanova JL. J Exp Med. 2018 PMID: 30068544
  • Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency. Kong XF*, Martinez-Barricarte R*, Kennedy J, Mele F, Lazarov T, Deenick EK, Ma CS, Breton G, Lucero KB, Langlais D, Bousfiha A, Aytekin C, Markle J, Trouillet C, Jabot-Hanin F, Arlehamn CSL, Rao G, Picard C, Lasseau T, Latorre D, Hambleton S, Deswarte C, Itan Y, Abarca K, Moraes-Vasconcelos D, Ailal F, Ikinciogullari A, Dogu F, Benhsaien I, Sette A, Abel L, Boisson-Dupuis S, Schröder B, Nussenzweig MC, Liu K, Geissmann F, Tangye SG, Gros P, Sallusto F, Bustamante J, Casanova JL. Nat Immunol. 2018 PMID: 30127434 *equal contributions